534-05STGD2461 T→AW821RMissense4139 C→TP1380LMissense5682 G→CNoneSilent5814 A→GNoneSilent

ABCA4

Case 2A 19-year-old female referred for consultation for difficulty reading, particularly in dim light. She was clinically diagnosed with STGD 3 month prior, after complaining of gradual difficulty in focusing. Family history was not significant for ocular disease. Visual acuity measured 20/40 OD and 20/150 OS. Slit-lamp examination was unremarkable with normal anterior segments and applanation tensions of 14 mmHg OU. Funduscopic exam revealed bilateral central atrophy, multiple fleck lesions, multiple clumps of yellowish deposits at the level of the retinal pigment epithelium in the posterior pole surrounded with some pigment clumping, and no evidence of atrophy of the retinal pigment epithelium. Autofluorescence imaging revealed multifocal atrophic lesions involving the central macula and peripheral hyperautofluorescent flecks OU. The peripapillary regions demonstrated atrophic flecks OU without confluent atrophy (Figure 2, A and B). Genotyping revealed homozygous ABCA4 mutations, P1380L and P1380L.Open in a separate windowFig. 2Case 2. STGD mutations P1380L and P1380L. A, Autofluorescence OD. B, Autofluorescence OS show multifocal hypoautofluorescent (atrophic) lesions involving the central macula OU and peripheral hyperautofluorescent flecks OU. The peripapillary regions have atrophic flecks OU but there is not confluent peripapillary atrophy.

Case 4A 52-year-old male was examined for declining vision OS over the past few months. He was previously clinically diagnosed with STGD 7 years before presentation. Family history was not significant for ocular disease. Best-corrected visual acuity measured 20/100 OD and 20/70 OS. Spherical refractive error measured −3.00 OD and −3.25 OS. Anterior segment examination was unremarkable and applanation tonometry measured 17 mmHg OD and 14 mmHg OS. Posterior segment examination was significant for central atrophy and classic peripheral pisciform flecks sparing the peripapillary regions OU (Figure 4, A and B). Autofluorescence imaging demonstrated inner atrophic flecks and outer hyperautofluorescent flecks. Moderate peripapillary hypoautofluorescence, but not atrophy, was present, likely secondary to the patient’s myopia (Figure 4, C and D). Genotyping revealed two heterozygous ABCA4 mutations, P1380L and S1696N.Open in a separate windowFig. 4Case 4. STGD mutation IVS40 + 5G>A. A, Color Photo OU. B, Red-Free Photo OU reveal central atrophy and classic peripheral pisciform flecks sparing the peripapillary regions OU. C, Autofluorescence OD. D, Autofluorescence OS show that the innermost flecks are hypoautofluorescent, consistent with atrophy, whereas the outermost flecks are hyperautofluorescent, demonstrating excess lipofuscin. There is moderate peripapillary hypoautofluorescence that is not as dark as this patient’s central atrophy or the peripapillary atrophy of Case 1. This finding may thus be due to the patient’s myopia.

A 25-year-old White man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid.

Case 1A 55-year-old male was examined for long-standing central visual impairment since age 18. Family history was not significant for ocular disease. His best-corrected visual acuity of 20/350 OD and 20/200 OS was consistent with measurements over the last 20 years. Spherical refractive error measured −3.5 OD and −2.0 OS. Anterior segment examination was unremarkable and applanation tonometry measured 17 mmHg OD and 14 mmHg OS. Posterior segment examination and autofluorescence imaging were significant for sharply demarcated central and peripapillary zones of atrophy and the absence of fleck lesions (Figure 1, A–D). Humphrey visual fields demonstrated bilateral central scotomas with eccentric fixation at the inferior border. ERG examination was subnormal and similar to results obtained 22 years ago.Open in a separate windowFig. 1Case 1. STGD with peripapillary atrophy and mutations P1380L and IVS40 + 5G>A. A, Autofluorescence OD. B, Color Photo OD. C, Autofluorescence OS. D, Color Photo OS. All show marked peripapillary and macular atrophy with a sharply demarcated zone of sparing between them. These characteristics caused initial diagnostic confusion with choroidal sclerosis.Genetic testing was employed for further diagnostic information and two heterozygous ABCA4 mutations, P1380L and IVS40 + 5G>A, were identified and classified as disease-causing alleles, thereby confirming the diagnosis of STGD.

Case 4A 52-year-old male was examined for declining vision OS over the past few months. He was previously clinically diagnosed with STGD 7 years before presentation. Family history was not significant for ocular disease. Best-corrected visual acuity measured 20/100 OD and 20/70 OS. Spherical refractive error measured −3.00 OD and −3.25 OS. Anterior segment examination was unremarkable and applanation tonometry measured 17 mmHg OD and 14 mmHg OS. Posterior segment examination was significant for central atrophy and classic peripheral pisciform flecks sparing the peripapillary regions OU (Figure 4, A and B). Autofluorescence imaging demonstrated inner atrophic flecks and outer hyperautofluorescent flecks. Moderate peripapillary hypoautofluorescence, but not atrophy, was present, likely secondary to the patient’s myopia (Figure 4, C and D). Genotyping revealed two heterozygous ABCA4 mutations, P1380L and S1696N.Open in a separate windowFig. 4Case 4. STGD mutation IVS40 + 5G>A. A, Color Photo OU. B, Red-Free Photo OU reveal central atrophy and classic peripheral pisciform flecks sparing the peripapillary regions OU. C, Autofluorescence OD. D, Autofluorescence OS show that the innermost flecks are hypoautofluorescent, consistent with atrophy, whereas the outermost flecks are hyperautofluorescent, demonstrating excess lipofuscin. There is moderate peripapillary hypoautofluorescence that is not as dark as this patient’s central atrophy or the peripapillary atrophy of Case 1. This finding may thus be due to the patient’s myopia.

Case 1A 55-year-old male was examined for long-standing central visual impairment since age 18. Family history was not significant for ocular disease. His best-corrected visual acuity of 20/350 OD and 20/200 OS was consistent with measurements over the last 20 years. Spherical refractive error measured −3.5 OD and −2.0 OS. Anterior segment examination was unremarkable and applanation tonometry measured 17 mmHg OD and 14 mmHg OS. Posterior segment examination and autofluorescence imaging were significant for sharply demarcated central and peripapillary zones of atrophy and the absence of fleck lesions (Figure 1, A–D). Humphrey visual fields demonstrated bilateral central scotomas with eccentric fixation at the inferior border. ERG examination was subnormal and similar to results obtained 22 years ago.Open in a separate windowFig. 1Case 1. STGD with peripapillary atrophy and mutations P1380L and IVS40 + 5G>A. A, Autofluorescence OD. B, Color Photo OD. C, Autofluorescence OS. D, Color Photo OS. All show marked peripapillary and macular atrophy with a sharply demarcated zone of sparing between them. These characteristics caused initial diagnostic confusion with choroidal sclerosis.Genetic testing was employed for further diagnostic information and two heterozygous ABCA4 mutations, P1380L and IVS40 + 5G>A, were identified and classified as disease-causing alleles, thereby confirming the diagnosis of STGD.

A10M c.4139C>T:p(P1380L